The present invention is directed to the treatment of various chronic and acute skin conditions, particularly acne and photoaging.
There is presently in use an FDA approved treatment for acne employing tazarotene topical gel that is marketed by Allergan, Inc. under the brand name Tazorac.TM..
Tazarotene has the following chemical formula: ##STR1## and is described by the chemical name: ethyl 6-[2-(4,4-dimethylthiochroman-6-yl)-ethynyl nicotinate. (C.sub.21 H.sub.21 NO.sub.2 S). Tazorac.TM. gel is commercially available in 0.05% and 0.1% formulations by weight of tazarotene, with 1.0% benzyl alcohol as a preservative and the following inactive ingredients: ascorbic acid, butylated hydroxyanisole, butylated hydroxytoluene, carbomer 934P, edetate disodium, hexylene glycol, purified water, poloxamer 407, polyethylene glycol 400, polysorbate 40, and tromethamine.
Tazarotene is a retinoid prodrug which is converted to its active form--the cognate carboxylic acid of tazarotene (AGN 190299)--by rapid deesterification in most biological systems. AGN 190299 binds to all three members of the retinoic acid receptor (RAR) family; RAR.sub..alpha. RAR.sub..beta. and RAR.sub..gamma., but shows relative selectivity for RAR.sub..beta. and RAR.sub..gamma., and may modify gene expression. The clinical significance of these findings is not known.
The mechanism of action in the treatment of acne and photoaging with tazarotene is not known. The current FDA-approved therapeutic regimen requires Tazorac.TM. gel to be applied topically in its 0.05% or its 0.1% formulation and left on the affected skin for long periods of time, e.g. overnight. It is generally applied in the evening and left in place until routine washing in the morning. Thus, in the treatment of acne, the Tazorac.TM. gel would typically be left on the skin for 8 to 12 hours.
Unfortunately, a major shortcoming of this course of treatment is that adverse skin reactions are experienced by a significant portion of users. These reactions include pruritus, burning/stinging and erythema (sometimes severe). Since the treatment regimen is usually prolonged, covering many weeks or months, any adverse reactions are rendered even more substantial in the perception of the user, often resulting in the interruption or abandonment of the treatment regimen. Thus the adverse reactions are not merely significant in-and-of themselves, but may make treatment ineffectual due to the inability or unwillingness of the user to follow the regimen.